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Anthropogenic litter, such as plastic, is investigated by the global scientific community from various fields employing diverse techniques. The goal is to assess and finally mitigate the pollutants' impacts on the natural environment. Plastic litter can accumulate in different matrices of aquatic and terrestrial ecosystems, impacting both biota and ecosystem functioning. Detection and quantification of macroplastics, and other litter, can be realized by jointly using visual census and remote sensing techniques. The primary objective of this research was to identify the most effective approach for monitoring macroplastic litter in riverine and marine environments through a comprehensive survey based on the experiences of the scientific community. Researchers involved in plastic pollution evaluated four litter occurrence and flux investigation methods (visual census, drone-based surveys, satellite imagery, and GPS/GNSS trackers) through a questionnaire. Traditional visual census and drone deployment were deemed as the most popular approaches among the 46 surveyed researchers, while satellite imagery and GPS/GNSS trackers received lower scores due to limited field validation and short performance ranges, respectively. On a scale from 0 to 5, visual census and drone-based surveys obtained 3.5 and 2.0, respectively, whereas satellite imagery and alternative solutions received scores lower than 1.2. Visual and drone censuses were used in high, medium and low-income countries, while satellite census and GPS/GNSS trackers were mostly used in high-income countries. This work provides an overview of the advantages and drawbacks of litter investigation techniques, contributing i) to the global harmonization of macroplastic litter monitoring and ii) providing a starting point for researchers and water managers approaching this topic. This work supports the selection and design of reliable and cost-effective monitoring approaches to mitigate the ambiguity in macroplastic data collection, contributing to the global harmonization of macroplastic litter monitoring protocols., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Coastal wetlands represent areas that can testify historical accumulation of litter. We analyzed the anthropogenic litter deposited on the channel bottom of a coastal wetland area that experienced water stress due to extreme summer dryness after about 20 years. We hypothesize that the litter accumulated in the different areas over the years reflects the different social user categories (i.e., fishermen, beach users, hunters) and exposure to meteo-marine events. Our findings highlight that historically accumulated litter is composed of plastics (78.8 %), clothes (8.9 %), and glass (4.9 %). Moreover, litter concentration averages 53.6 items/ha in the 8 sectors. The most found categories were common household items (25.4 %), diverse (professional and consumer) items (24.2 %), and food and beverages packaging (21.4 %). Finally, litter diversity indices and the Detrended Correspondence Analysis showed sector and litter type similarities. We reported for the first time the presence of litter accumulated for 20 years testifying non-more occurring recreational activities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Anthropogenic litter accumulates along coasts worldwide. In addition to the flowing litter load, wind, sea currents, geomorphology and vegetation determine the distribution of litter trapped on the sandy coasts. Although some studies highlighted the role of dune plants in trapping marine litter, little is known about their efficiency as sinks and about the small-scale spatial distribution of litter across the dune area. Here, we explore these gaps by analysing six plant species widespread in Mediterranean coastal habitats, namely Echinophora spinosa, Limbarda crithmoides, Anthemis maritima, Pancratium maritimum, Thinopyrum junceum, and Salsola kali. The present study analyses for the first time the capture of litter by dune vegetation at a multi-species level, considering their morphological structure. Data on plastic accumulation on dune plants were compared with unvegetated control plots located at embryo-dune and foredune belts. We found that dunal plants mainly entrapped macrolitter (> 0.5 cm). Particularly, E. spinosa, L. crithmoides, A. maritima and P. maritimum mostly accumulated litter in the embryo dune while T. junceum and S. kali entrapped more in the foredune area. Moreover, beach litter was mainly blocked at the edge of the plant patches rather than in the core, highlighting the 'Plant-edge litter effect'. As A. maritima and S. kali entrapped respectively more litter in embryo and foredune habitats, these species could be used to monitor and recollect litter. In this light, our findings provide further insight into the role of dune plants in the beach litter dynamics, suppling useful information for beach clean-up actions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

The ability to retain anthropogenic marine litter by a halo-psammophilous plant formation dominated by a single prostrate species (Salsola kali) on a Sardinian beach was measured. We hypothesized that the anthropogenic litter (i) is trapped by plants to a greater extent than in control areas, and (ii) has more elongated size, mimicking the organic Posidonia wrack, largely occurring locally as 'banquettes'. Salsola kali patches show an apparently higher anthropogenic litter density than control sites without vegetation. Salsola kali plants trap litter items significantly longer and a larger number of size length categories than control plots. These effects may be due to the prostrate structure of the plant with small thorns at the apex. Also, litter entrapped by plants can interfere with the mechanisms of dune deposition and structuration, in turn affecting food chains by decreasing the availability of organic material for pedofauna., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Coastal vegetation intercepts macroplastics and, consequently, it may represent a reservoir of anthropogenic litter and organic wrack. We aimed at investigating (i) the abundance variation of macrolitter from the beach to foredune and backdune (three cross-shore plots over 20 long-shore sectors) and (ii) the role of the halo-psammophilous plants and Phragmites australis reedbed in intercepting the macrolitter, respectively, in the foredunes and backdunes. The vegetation in the foredunes (mainly halo-psammophilous species) acted as a first interception belt for macrolitter, while the bigger litter reached the backdunes. Our results might be of great concern with implications for beach clean-ups - which must also be mainly focused in foredunes and backdunes, however warning operators in advance that they could damage the vegetation by trampling on., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Fishing lines, hooks and nets represent a sub-category of macro-litter potentially entrapping plover birds nesting on sandy beaches. Here, during a winter period, the accumulation pattern of both general beach litter and fishing lines, hooks and nets was analysed on four central Italy beaches. Despite the active monthly litter removal by clean-ups, there was not a decrease in its density during the winter period, due to the continuous accumulation by frequent winter storms. However, the entrapping litter was very low (<2.5 % of the general litter) and appeared directly correlated to the general litter density. Following a DPSIR approach, the general litter can act as an indirect pressure indicator (proxy) of the amount of entrapping litter. Therefore, an increase in general macro-litter should alarm those involved in the conservation of entanglement-sensitive bird species, such as plovers, suggesting that they should implement high-frequency clean-up activities aimed at removing it., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

We investigated the temporal changes from spring to summer of the stranded litter and the composition of plastic encrusting biota along an Italian beach. Our findings highlight a higher quantity of litter (average value 1510.67 ± 581.27 items) in spring, particularly plastic material with a composition driven by currents, winds and waves transported from rivers to sea. During summer the source was caused by anti-social behaviours (e.g. cigarettes). Regarding the plastic size, the most is macroplastic (85.96 %), followed by mesoplastic (13.74 %) and megaplastic (0.30 %) overall, and no seasonal trend was observed. Concerning the encrusting biota, Mollusca was the most frequent phylum found on plastic beach litter, whereas Porifera the most abundant overall. During spring a greater abundance of individuals was recorded compared to summer. The trend of taxa richness was decreasing from spring to summer. Arthropoda, Porifera and Mollusca phyla were significantly more abundant in spring, while Algae in summer., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Dunal plants may affect the patterns of deposition of beach litter. In this study, we aimed at evaluating if Carpobrotus spp. patches may act as a litter trap in coastal dune systems. To do so, we counted the number of macrolitter occurring in both Carpobrotus and control (embryo dune vegetation) patches classifying each item into categories according to the Marine Strategy. Totally, we observed a significant difference between litter trapped in Carpobrotus (331 items, representing 62.4% of the total beach litter) and control (199, 37.6%). Plastic fragments were the most trapped items by both Carpobrotus (46.2%) and control patches (47.2%). We also calculated the item co-occurrence, obtaining a random aggregated 'litter community'. The main emerging output is that Carpobrotus patches act as filter in respect to different anthropogenic materials (overall plastics), suggesting that alien plant management actions may contribute to solve beach litter issues as well., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

We investigated the accumulation of litter along a transition gradient from the dunal beaches (B), to the backdunes (BD), to the channels of a coastal wetland (W), considering both the total litter and a sub-category represented by expanded polystyrene (EPS). Using a removal sampling technique carried out in spring (April and May), we hypothesized that: (i) the total accumulation of litter decreases progressively from the dunes to the backdunes to wet environments while (ii) the lighter polystyrene concentrates in the BD-W fringe where the Phragmites australis reedbeds can have a sink role for this polymer. The total litter density showed a significant decrease along the gradient B-BD-W in both months, with an evident collapse between BD and W. Analogously, EPS showed a significant difference in density along the B-BD-W gradient in both months, although with a different pattern: a maximum in the BD and a significant collapse between BD and W. The presence of backdune hygrophilous vegetation (Phragmites australis' reedbeds) may act as a sink trapping all types of litter in both cases (total litter and EPS). The different accumulation pattern between total litter and the EPS is due to the lower specific weight of the latter polymer: while the generic litter tends to decrease quantitatively moving away from the sea, the lighter EPS is removed by the winds and pushed towards the land, beyond the dune, where it is trapped by the vegetation, thus showing a peak in density in the backdunes. No significant differences were observed between the litter density in the two months (before and after the removal) either considering the total litter and only EPS. This may suggest a continuous supply of litter from the sea, highlighting how clean-ups actions should be carried out with a higher frequency rather than monthly. This may be even more valid in the period of greater frequency of intense weather-marine events (autumn-winter) when a greater quantity of litter is deposited. These are the first data for the Mediterranean regarding a specific role of wetland hygrophilous vegetation as a sink for anthropogenic litter, mainly expanded polystyrene., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

This study analyzes the occurrence and distribution of plastic litter and the entrapment of plastic by wrack beached on a natural reserve. Large microplastics (2.5 - 5 mm) were the most abundant plastic size category detected. The main color and shape were white and fragment, respectively. The plastics entrapped by egagropiles were mainly transparent fibers. We analyzed the correlation between the weights of plastic litter and vegetal wrack in two transects, selected for their different environmental characteristics. The transect closer to a breakwater showed a significant positive correlation between the weights of plastics and wrack, while the other transect suggested a casual pattern of plastic deposition on the beach. Further research is suggested to focus on the role of breakwaters in altering marine currents and enhancing plastic beaching., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Despite declaration as a national priority disease, dog rabies remains endemic in Liberia, with surveillance systems and disease control activities still developing. The objective of these initial efforts was to establish animal rabies diagnostics, foster collaboration between all rabies control stakeholders, and develop a short-term action plan with estimated costs for rabies control and elimination in Liberia. Four rabies diagnostic tests, the direct fluorescent antibody (DFA) test, the direct immunohistochemical test (dRIT), the reverse transcriptase polymerase chain reaction (RT-PCR) assay and the rapid immunochromatographic diagnostic test (RIDT), were implemented at the Central Veterinary Laboratory (CVL) in Monrovia between July 2017 and February 2018. Seven samples (n=7) out of eight suspected animals were confirmed positive for rabies lyssavirus, and molecular analyses revealed that all isolates belonged to the Africa 2 lineage, subgroup H. During a comprehensive in-country One Health rabies stakeholder meeting in 2018, a practical workplan, a short-term action plan and an accurately costed mass dog vaccination strategy were developed. Liberia is currently at stage 1.5/5 of the Stepwise Approach towards Rabies Elimination (SARE) tool, which corresponds with countries that are scaling up local-level interventions (e.g. dog vaccination campaigns) to the national level. Overall an estimated 5.3 - 8 million USD invested over 13 years is needed to eliminate rabies in Liberia by 2030. Liberia still has a long road to become free from dog-rabies. However, the dialogue between all relevant stakeholders took place, and disease surveillance considerably improved through implementing rabies diagnosis at the CVL. The joint efforts of diverse national and international stakeholders laid important foundations to achieve the goal of zero dog-mediated human rabies deaths by 2030., (Copyright © 2020. Published by Elsevier B.V.)

In order to maintain the hydraulic outflow in land reclaimed canalizations, the competent agencies provide to mechanically mow the Giant Reed (Arundo donax, L. 1753) along the aquatic ecosystem banks. Nevertheless, the reeds mowed can be transported away from the waters following storm surges and can be deposited in large quantities along the sandy beaches. We carried out a stratified study in a Mediterranean sandy beach to test the hypothesis that Giant Reed wrack may act as a sink and barrier for plastic beach litter. We observed a large amount of plastic litter entrapped in the Arundo donax wrack (density of 0.868 items/m 2 ), with a higher density when compared to both the inner and the shoreline belts. Density of litter is significantly higher considering the categories of meso- and micro-plastics. Organic macrophyte wrack is useful for dunal macrodetritivorous invertebrates and generally for fauna communities, which use this litter as refuge and trophic pabulum. Significant accumulations of organic wrack can mitigate coastal erosion; nevertheless, for its structural characteristics, Arundo wrack can also act as a barrier for litter towards the inner vegetated dunes, so entrapping a large amount of anthropogenic litter. In this regard, Arundo wrack can represent a sink habitat, first attracting (due to large availability of detritus with a relative high rate of decomposition) and then, entrapping many organisms in anthropogenic litter. We suggest that, once mechanically mowed, the land reclaimed agencies should periodically remove from the channel banks the Arundo donax reeds, impeding the accumulation of incoherent vegetated matter along the aquatic ecosystem banks., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

This note reports data about a heterogeneous assemblage of anthropogenic litter recorded in 307 nesting and roosting sites of Yellow-legged Gull (Larus michahellis) from a small Mediterranean island. I obtained items of anthropogenic litter on > 30% on the total, with plastic, glass and paper the significantly more abundant litter categories. Litter items were found in the nests mainly as a dry remnant in the regurgitated pellets. Fragments of expanded polystyrene (EPS) with peck marks were also recorded, these last transported to the nests because of their resemblance to the cuttlebones of the Sepia cuttlefish. Ingestion of this litter and the pecking on EPS can negatively impact on seabirds. Moreover, the presence of this litter highlights a transport of polluting material even at considerable distance from anthropized areas. Finally, the presence of scavenger species (an endemic lizard and terrestrial molluscs) feeding on food remains could suggest an assimilation of litter into the trophic webs., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The interaction of anthropogenic litter (by incorporation litter in nests, ingestion, and entanglement) with birds was systematically reviewed using Google Scholar database. A 'black-list' of 258 species was compiled. Among them 206 (79.8%) were seabirds. Four seabird orders (Gaviiformes, Phaetontiformes, Procellariformes, Sphenisciformes) showed the highest percentage of interacting species. At family level, >70% of species of Gaviidae, Diomedeidae, Sulidae, Stercoraridae and Alcidae were involved in interactions with litter. We observed (i) a significant correlation between Scholar recurrences and species citations about anthropogenic litter only when considering seabirds; (ii) a low number of references before 1981 with a bimodal pattern showing a first peak in 1986-90 and a progressively increasing trend in the 2000s. Regarding the type of interaction, there was a significantly higher percentage of species involved in ingestion when compared to the percentage involved in entanglement. We suggest the use of consolidated standardized litter nomenclature and characterization and the adoption of a logical causal chain helping researchers in defining suitable frameworks., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Several single gene disorders can potentially be overlooked in the differential diagnostic evaluation of patients with multiple sclerosis (MS). Pelizaeus-Merzbacher disease and spastic paraplegia type 2 are allelic X-linked disorders associated with defective myelination of the central nervous system and mutations in PLP1. Neurological symptoms are occasionally observed in female carriers of these mutations. Two women - the proposita (Pt1) and her mother (Pt2) - reported walking difficulties since adolescence and showed progressive cognitive decline. Their neurological examinations revealed spastic gait, pyramidal tract involvement and distal muscle atrophy in the legs. Peripheral neuropathy and diffuse white matter (WM) changes on brain MRI were also observed. Both patients had a preliminary diagnosis of primary progressive MS. Using a targeted method in next generation sequencing, the novel heterozygous c.210T>G/p.Y70* in PLP1 was identified in Pt2. The same mutation was also found in Pt1 but not in five healthy relatives. The mutation showed moderate-to-severe skewed X inactivation in tissues, and Western blotting revealed a significant reduction of PLP1 and DM20 in the sural nerve of Pt2. In conclusion a mother and daughter presented an X-linked dominant disorder with skewed X inactivation. The authors suggest that PLP1 testing might be considered in the evaluation of women with spastic paraparesis, cognitive decline and WM changes., (Copyright © 2017 Elsevier B.V. All rights reserved.)

We assessed the annual accumulation rates of beach litter on the Tyrrhenian coast of central Italy, providing the characterization of litter following European standardized guidelines. Three different sites of a beach were sampled seasonally from spring 2014 to winter 2015. A total of 31,739 items were removed and classified into 103 categories. Plastic represented the majority (94.4%) of the collected items. We detected temporal and spatial differences in the abundance and composition of litter between seasons and between sites. Furthermore, we found that plastic cotton bud sticks composed >30% of the total amount of litter and, together with plastic and polystyrene pieces, made up >70% of the total items. Finally, our results led us to propose that the most effective strategy to reduce litter pollution is to devise specific management procedures focusing on the most abundant items., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: POLG-related disorders are a group of heterogeneous diseases characterized by an overlapping clinical presentations and associated with mutations in the POLG gene. POLG codes for the catalytic subunit of mitochondrial polymerase gamma (POLG), essential for mitochondrial DNA (mtDNA) replication and repair. Studies on mutator POLG mice showed an increase in oxidative stress and apoptosis. In this regard we analysed the involvement of POLG mutations in the apoptotic regulation, evaluating apoptosis in peripheral blood lymphocytes (PBLs) from patients with POLG-related diseases., Methods: Cells were cultured under basal conditions and with 2-deoxy-d-ribose (dRib), a reducing sugar that induces apoptosis by oxidative stress. Apoptosis rate was assessed by flow cytometry. Phosphatidylserine translocation, mitochondrial membrane depolarization and caspase 3 activation were also analysed., Results: Our data showed higher percentages of apoptosis after dRib treatment in patients with POLG mutations than in controls, while under basal culture conditions, apoptosis levels were similar in the two groups., Conclusions: Cells with POLG mutations are more sensitive than control cells to oxidative stress-induced apoptosis, confirming that mtDNA mutations may have a role in mitochondrial apoptosis pathway. We also suggest that redox state homeostasis may play a crucial role in phenotypic expression of POLG-related diseases., (Copyright © 2016. Published by Elsevier B.V.)

Autosomal dominant optic atrophy (ADOA) is a hereditary optic neuropathy characterized by bilateral symmetrical visual loss, decrease in retinal ganglion cells and a loss of myelin within the optic nerve. ADOA is associated to mutations in Optic atrophy 1 gene (OPA1), which encodes a mitochondrial protein involved in cristae remodeling, maintenance of mitochondrial membrane integrity, mitochondrial fusion and apoptosis regulation. We thus evaluated the rate of apoptosis and the expression levels of OPA1 isoforms in ADOA and control cells. Peripheral blood lymphocytes from eight patients with OPA1 mutation and age matched controls were cultivated both in basal conditions or with 2-deoxy-D-ribose, a reducing sugar that induces apoptosis through oxidative stress. Apoptosis was analyzed by flow cytometry, phosphatidylserine translocation, mitochondrial membrane depolarization and caspase 3 activation. We also analyzed the expression levels of OPA1 isoforms in ADOA and control cells cultured with and without 2-deoxy-D-ribose. We showed an increased percentage of apoptotic cells in ADOA patients compared to controls, both in basal culture conditions and after 2-deoxy-D-ribose treatment. This suggested a great susceptibility of ADOA cells to oxidative stress and a strong correlation between OPA1 protein dysfunctions and morphological-functional alterations to mitochondria. Moreover OPA1 protein expression was significantly decreased in lymphocytes from the ADOA patients after 2-deoxy-D-ribose treatment, implying a great sensitivity of the mutated protein to free radical damage. Concluding, we could confirm that oxidative stress-induced apoptosis may play a key role in the pathophysiological process bringing to retinal ganglion cells degeneration in ADOA., (Copyright © 2015. Published by Elsevier B.V.)

Sandy shores are generally considered important sinks for marine litter and the presence of this litter may represent a serious threat to biotic communities and dune integrity mostly due to cleaning activities carried out through mechanical equipment. In spring (April-May) 2012 we sampled 153 2×2m random plots to assess the spatial distribution patterns of litter on Central Italy sandy shores. We analysed the relationship between the presence of litter and coastal dune habitats along the sea-inland gradient. Our results showed that the most frequent litter items were plastic and polystyrene. Differences of marine litter spatial distribution were found between upper beach and fore dune habitats and fixed dune habitats: embryo dune and mobile dune habitats show the highest frequency of litter, but, surprisingly, marine litter did not impact fixed dune habitats, these possibly acting as a natural barrier protecting the inner part of the coast from marine litter dispersion., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The 3243A>G mutation of mtDNA usually is associated with MELAS syndrome. Here we report a patient with the 3243A>G mutation presenting only recurrent muscle fatigue and elevated levels of serum creatine kinase (CK). The mother of the proband was referred to us for type 2 diabetes mellitus, muscle pain and sensorineural hearing loss. The percentage of mutation load in different tissues was similar in both subjects, except in the urinary epithelium. The mutation load in the son's urinary epithelial cells (UEC) was consistently higher (nearly 50%) than in his muscle (nearly 20%). We conclude that a correlation between the proportion of the UEC mutation load and the severity of the disease was lacking in this pedigree. The use of UEC as the tissue of choice in the noninvasive diagnosis of the 3243A>G mutation offers a very attractive alternative to muscle biopsy. Finally, our data expand the clinical spectrum of the 3243A>G mutation., (Copyright © 2014 Elsevier B.V. All rights reserved.)

We report a new T8306C transition in the D-stem of the MTTK gene of a 67-year-old man who manifested severe adult onset myopathy, myoclonus, leukoencephalopathy, neurosensory hypoacusis, hypertrophic cardiomyopathy and insulin resistance. No other family member was affected, suggesting that our patient was a sporadic case. The T8306C mutation was heteroplasmic in several tissues of the proband, while it was absent from his asymptomatic siblings. Single fibre analysis confirmed the segregation of higher mutational load in cytochrome c oxidase-deficient fibres. The mutation T8306C is predicted to disrupt a highly conserved base pair and was not found in more than 120 controls. This finding broadens the phenotypic and molecular spectrum of mitochondrial tRNA(Lys) associated disorders., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Alagille syndrome (AGS) is an autosomal dominant disorder characterized by cholestasis, cardiac, skeletal and ocular abnormalities. Increasing importance is being given to vascular and central nervous system impairment. AGS is in most cases caused by heterozygous mutations in the Jagged-1 (JAG1) gene encoding a cell-surface ligand of the Notch receptors. The interaction between Notch1 and JAG1 induces proliferation and inhibits apoptosis. We evaluated the role of apoptosis in AGS patients carrying a truncating mutation in exon 7 of JAG1. Peripheral blood lymphocytes (PBLs) from two patients were exposed to 2-deoxy-d-ribose (dRib). Apoptosis was analyzed by flow cytometry, fluorescence microscopy and Western blotting. PBLs from patients showed a significantly higher percentage of apoptosis than controls both in standard culture conditions and after dRib treatment, however we demonstrated a lack of caspase-8 activation in those cells. Our results confirm that JAG1 may play a role in apoptosis regulation. In particular, truncating mutations in JAG1 could lead to Notch signaling inhibition and determine a deregulation of survival and proliferation, favoring apoptosis. Moreover, the lack of caspase-8 activation in AGS patients indicates a possible selective impairment of caspase-8 cleavage suggesting that JAG1 plays a specific role in the regulation of caspase-8 activation., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: Mitochondrial diseases due to mitochondrial tRNA genes mutations are usually multisystem disorders with infantile or adult onset., Objective: To identify the molecular defect underlying a mitochondrial encephalomyopathy., Methods/patients: Case report of a 51year-old woman presenting with late-onset myoclonic epilepsy plus additional features. Proband's mother presented hypothyroidism and diabetes., Results: Muscle biopsy showed mitochondrial changes. Respiratory chain activities were reduced. The novel G5538A mutation was identified in different tissues DNAs from the proband and from her mother., Conclusion: We were able to identify a novel mtDNA tRNA((Trp)) gene pathogenic mutation., (Copyright 2010 Elsevier B.V. All rights reserved.)

Neuromyotonia(NMT) or Isaacs syndrome is a rare syndrome characterized by continuous spontaneous muscle fiber contraction resulting from hyperexcitability of peripheral nerves often associated with autoimmune disorders and tumours. Here we report an unpublished association of NMT and bladder cancer.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary form of small vessel disease in which the pons may show lacunar infarcts and leukoaraiosis. Acute pure vestibular syndrome may be due to caudal pontine lesions and is probably underestimated. We describe a case of CADASIL with acute vestibular syndrome mimicking peripheral vestibulopathy, and evidence of focal infarction in the ponto-medullary junction at gadolinium-enhanced MRI including diffusion-weighted imaging, involving the area of the right vestibular nucleus and root entry zone of the ipsilateral vestibular nerve bundle. In CADASIL, both focal brainstem lesions and leukoaraiosis may parallel supratentorial white matter changes and may be related to poor outcome. Their actual extent should be evaluated in longitudinal studies that might predict clinical outcome and progression of disability.

A new association of Vanishing White Matter (VWM) and premature ovarian failure (POF) was recently described as a sole entity called ovarioleukodystrophy. Seven out of eight patients reported by Fogli et al. had translation initiation factor (eIF2B) mutations, specific to the VWM. The only patient without mutations had a distinctive neurological presentation that included cognitive deterioration without motor signs and white matter abnormalities restricted to the frontal lobe. We describe here a case suggestive of ovarioleukodistrophy carrying no eIF2B mutations.

Alpha-synuclein has been implicated in the pathology of certain neurodegenerative diseases, including Parkinson disease (PD). Although the precise physiological and pathological role of alpha-synuclein is unclear, overexpression of the protein or its mutants may reduce cell viability. In this study we evaluated the apoptotic response to oxidative stress induced by 2-deoxy-d-ribose (dRib) in peripheral blood lymphocytes (PBLs) of two siblings with Parkinson disease secondary to A53T alpha-synuclein mutation. PBLs exposed to oxidative stress showed a higher percentage of apoptotic cells in PD patients than in controls. However in cells of PD patients, the increase of apoptotic response was lower than in controls, suggesting that cells of PD patients have greater "resistance" to oxidative stress. We conclude that other environmental agents could play a key role in inducing programmed cell death in cells of PD patients with mutant alpha-synuclein.

Background: Congenital heart disease is often severe and outcome remains uncertain. In some cases, early intervention at birth can improve the prognosis. Prenatal detection of congenital heart disease by ultrasound may improve outcome for foetuses with congenital heart disease but today, results are not convincing. The purpose of this review was to describe the detection of congenital heart disease in a non selected population., Methods: A retrospective study was undertaken to evaluate the prenatal detection of congenital heart disease in our department from 1984 to 2003., Results: Incidence of congenital heart disease was 4.9. Sensitivity of detection was 60%, specificity was 99.9%. Most cases were severe heart diseases. In 57 fetuses (40%), congenital heart disease was not detected. Thirty-seven fetuses (65%) presented minor disease; in 20 fetuses (35%), congenital heart disease was found to be severe. Effectiveness of detection of major congenital heart diseases has increased since 2000., Conclusion: Large-scale fetal heart screening is necessary for early detection of congenital heart disease and improved outcome.

Despite the identification of mutations in the methyl CpG binding protein 2 gene, the pathogenesis of Rett syndrome (RS) is still unknown. In order to clarify the role of apoptosis in this disorder, we studied lymphoblastoid cell lines in five classical RS patients and five controls, incubated with 2-deoxy-d-ribose (dRib), a reducing sugar that induces apoptosis in human cells, through oxidative damage. The apoptotic response was detected by flow cytometric analysis and agarose gel electrophoresis. The cells of RS patients showed a lower percentage of apoptosis in a routine condition than those of controls did, whereas, in the presence of dRib, the percentage of apoptotic cells in RS patients increased with time and reached the same percentage of those of controls at 72 h. The data observed here suggest that RS may have a low susceptibility or an increased resistance to the apoptotic cell death, which may be corrected only in the presence of a strong apoptotic stimulus.

We analyzed Niemann-Pick type C disease 1 (NPC1) gene in 12 patients with Niemann-Pick type C disease by sequencing both cDNA obtained from fibroblasts and genomic DNA. All the patients were compound heterozygotes. We found 15 mutations, eight of which previously unreported. The comparison of cDNA and genomic DNA revealed discrepancies in some subjects. In two unrelated patients carrying the same mutations (P474L and nt 2972del2) only one mutant allele (P474L), was expressed in fibroblasts. The mRNA corresponding to the other allele was not detected even in cells incubated with cycloheximide. The promoter variants (-1026T/G and -1186T/C or -238 C/G), found to be in linkage with 2972del2 allele do not explain the lack of expression of this allele, as they were also found in control subjects. In another patient, (N1156S/Q922X) the N1156S allele was expressed in fibroblasts while the expression of the other allele was hardly detectable. In a fourth patient cDNA analysis revealed a point mutation in exon 20 (P1007A) and a 56 nt deletion in exon 22 leading to a frameshift and a premature stop codon. The first mutation was confirmed in genomic DNA; the second turned out to be a T-->G transversion in exon 22, predicted to cause a missense mutation (V1141G). In fact, this transversion generates a donor splice site in exon 22, which causes an abnormal pre-mRNA splicing leading to a partial deletion of this exon. In some NPC patients, therefore, the comparison between cDNA and genomic DNA may reveal an unexpected expression of some mutant alleles of NPC1 gene.

The recently identified ATM gene plays a role in a signal transduction network activating multiple cellular functions in response to DNA damage. An attractive hypothesis is that the ATM protein is involved in a specialized antioxidant system responsible for detoxifying reactive oxygen intermediate and that the absence or dysfunction of this protein in AT cells would render them less capable of dealing with oxidative stress. In order to investigate the role of the ATM gene in cell cycle control and programmed cell death, Lymphoblastoid cell lines derived from four Ataxia-Telangiectasia (AT) patients and six controls have been analyzed. All cell lines were incubated with 2-deoxy-D-ribose (dRib), a reducing sugar that induces apoptosis through oxidative stress. The result showed an impaired response to dRib-induced apoptosis in AT cells, as well as a defect of cellular cycle arrest in G1/S phase and a normal expression of p53 protein. This indicate that the kinase activity of ATM gene product plays a very important role in the cellular response to oxidative stress. In conclusion the altered response of AT cells to oxidative stress and particularly their resistance to apoptotic cell death, could explain the high predisposition of these cells to progress toward malignant transformation.

The case of a 17-year-old girl with slowly progressive sensory-motor neuropathy is described. Sural nerve biopsy showed abnormally enlarged exons filled with neurofilaments. Neurofilament accumulation was limited to the axons and was not found in other cells of the skin or peripheral nerve. The patient showed EEG and brain MRI abnormalities, but there was no clinical evidence of central nervous system involvement. Although these findings suggest an atypical attenuated form of giant axonal neuropathy, a new nosological entity cannot be excluded.

The authors describe a case of early onset ataxia with cerebellar atrophy and vitamin E deficiency, treated with alpha-tocopherol supplementation and physically rehabilitated by postural biofeedback. Clinical assessments, serum vitamin E levels and postural evaluation by means of a stabilometric platform continued for about 2 years and significant clinical improvement was recorded. Our study confirms that combined physical therapy and vitamin E supplementation may result in improvement of cerebellar function. Motor improvement is directly related to vitamin E serum levels, providing further confirmation that normal vitamin E levels are crucial for proper brain functions.

In order to study the role of vitamin E in the pathogenesis of Rett syndrome (RS), we analysed vitamin E serum levels in twenty-eight patients affected by this disorder. We found lower vitamin E serum levels in nine cases (32.1%). These results indicated that the oxidative free radical metabolism may be impaired in a significant percentage of Rett syndrome patients suggesting the need for further studies of tissue vitamin E in different brain regions.

Perineurial cell ensheathment of muscle fibers has been reported only in one patient. Here we describe a new case with identical morphologic features and a similar, but milder clinical course characterized by progressive muscle weakness and bilateral palpebral ptosis. EMG examination (including repetitive stimulation) and antibodies against acetylcholine receptors were normal. Muscle biopsy revealed several muscle fibers encircled by stratified rings of homogeneous material in which elongated nuclei were visible; this material was positively stained by antibodies directed at epithelial membrane antigen. On ultrastructural examination these encircling-fiber spirals had the characteristics of perineurial cells. It is not clear yet whether perineurial cell ensheathment of muscle fibers is an occasional feature, or whether it has a pathogenetic role in the clinical picture of both cases. The perineurial sheaths might alter the correct neuromuscular transmission mimicking a myasthenia-like disease, either by interfering with the neuromuscular junction, or by changing the microenvironment, and, thus, altering the general excitability of the muscle fibers.

Ataxia-telangiectasia (AT) is an autosomal recessive disease characterized by neurodegeneration and immunodeficiency. Hypersensitivity to radiation and chromosome instability are the biological markers of this disease. The gene responsible for AT (ATM), has been identified on chromosome 11q22-23; it encodes a large polypeptide partially homologous to the phosphatidylinositol (PI) 3-kinase family. PI 3-kinase is a protein family playing an important role in the prevention of apoptosis. In order to investigate the apoptosis pathway, we tested peripheral blood cells from AT patients and controls exposed to 2-deoxy-D-ribose (dRib), a reducing sugar that induces apoptosis in human quiescent lymphocytes, probably through oxidative damage. Our results show that the response to dRib-induced apoptosis is significantly more elevated in AT cells than in control cells, suggesting that the apoptotic process plays a role in the pathogenesis of AT disease.

In order to study the role of vitamin E in the pathogenesis of ataxia telangiectasia, we analysed vitamin E serum levels in five children with this disorder. No differences with respect to controls were found. However, these negative results do not exclude that abnormal vitamin E metabolism may be present at the cellular level.

Amiodarone is effective in the treatment of supraventricular and ventricular cardiac arrhythmia, however a high incidence of toxic side effects has been observed in various organs and tissues during chronic treatment. Ultrastructural observation of affected tissues reveals myelinoid inclusion bodies. The exact pathogenetic mechanism of these changes is still unknown. In this study we investigated the biochemical effects of this drug on lysosomal hydrolases and the alterations induced in subcellular organelles of fibroblasts cultured for 24 h with different concentrations of amiodarone in the medium. Of the enzyme activities assayed, we only observed a significant reduction in sphingomyelinase. Ultrastructural observation of fibroblasts showed swollen lysosomes and a few onionoid inclusion bodies at lower concentrations of the drug; at higher concentrations the lysosomal system was severely impaired. Cytochemical staining of unesterified cholesterol with filipin showed accumulation of cholesterol. We conclude that chronic amiodarone treatment in experimental conditions induces inhibition in sphingomyelinase activity through interaction with membrane lipids and modification of bilayer structure. Higher concentrations of the drug impair cholesterol transport and induce lipid accumulation. These results may be useful for understanding the pathogenesis of induced lipidosis in patients in chronic treatment with amiodarone.

In recent years several synthetic peptides have been shown to be active in inducing GH secretion in different mammalian species. Among them GHRP-6, GHRP-1 and GHRP-2 have demonstrated high effectiveness and high selectivity in stimulating GH release. In the present paper we report studies on the GH-secreting properties of a GHRP analog in which Trp was substituted with the chemically more stable 2-Methyl-Trp. In studies performed in conscious 10-day old rats, the hexapeptide Hexarelin (His-D-2Me-Trp-Ala-Trp-D-Phe-Lys-NH2) resulted very active in stimulating GH secretion. In anesthetized adult male rats, i.v. administration of GHRP-6 or Hexarelin elicited prompt GH release with peak GH levels occurring within 10 min At all the doses tested, the 2 peptides possessed similar effectiveness in stimulating GH release. Hexarelin given s.c. elicited a long-lasting GH release and was slightly more effective than GHRP-6. In conclusion, these findings indicate that Hexarelin is a highly effective GH releaser and might represent a valuable diagnostic and/or therapeutic tool in clinical practice.

A large heterogeneous group of lysosomotropic compounds with a common cationic amphiphilic structure induces in vitro and in vivo lysosomal lipid storage. The biochemical mechanism underlying the lipidosis is still the subject of investigation. The authors report the experimental effect of imipramine and dexamethasone on lysosomal system in cultured skin fibroblasts. Morphological and ultrastructural observations of cells treated with imipramine showed vacuoles with lipidic storage, enlarged lysosomes with electron translucent zones and normal appearance of all the other cytoplasmic organelles. The lysosomal enzyme activities were decreased on biochemical study. On the contrary, an increased enzyme activity was detected in the culture medium. Pretreatment with dexamethasone partially prevented the effect of imipramine. Our results suggest that tricyclic antidepressants may induce lysosomal lipidosis through a dysfunction in the recycling of mannose-6-phosphate receptors and in the trafficking of newly synthesized lysosomal enzymes. Moreover the data presented may provide a clue in understanding some of the side effects observed in patients chronically treated with antidepressant drugs.